Since the outbreak in New York City in 1999, WNV has been rapidly spreading throughout North America and has caused thousands of deaths in the U.S.A. Infection is usually asymptomatic in most cases, but elicits fever, meningitis, encephalitis or acute flaccid paralysis in 20–40% of individuals. The mechanisms by which neurotropic flaviviruses including WNV enter the central nervous system are not well understood. In theory, WNV can enter the brain through many routes including 1) endothelial tight junctions, 2) direct infection of endothelial cells, 3) infected leukocytes that traffic to the CNS, 4) infection of olfactory neurons and 5) direct axonal retrograde transport from infected peripheral neurons. Although infiltrating CD8 T cells are crucial for controlling WNV dissemination in the CNS, they are recruited to the CNS too late after viral invasion to prevent initial infection. Early entry of neutrophils that carry a heavy load of neurotropic virus may be deleterious to host and contribute to CNS inflammation. Here, we studied the in vivo role of IL-22 in WNV infection and found that IL-22 contributed to the early entry of neutrophils into the CNS. Results show that IL-22 signaling contributes to WNV pathogenesis in the CNS. Systemic lupus erythematosus is a prototypic autoimmune disease affecting multiple tissues and organs with a diverse array of clinical manifestations. Among the wide variety of immunological aberrations associated with SLE, most prominent is the presence of auto-reactive T and B cells with specificity for self molecules commonly found in the nucleus, such as doublestranded DNA and RNA-containing small nuclear ribonucleoprotein. While T cell has long been considered as a major player in the pathogenesis of SLE, B cell abnormalities have received much attention in recent years, partly because of the remarkable success of B cell depletion as a treatment for SLE. Patients with active SLE have been found to have1.5–4-fold more IgG and IgM-secreting cells in the peripheral blood, with a concomitant increase in the number of B cells secreting autoantibodies, especially anti-DNA antibodies. Moreover, B cells from SLE patients exhibit augmented calcium response and increased tyrosine phosphorylation upon BCR crosslinking. The precise mechanisms underlying the altered B cell compartment in SLE remains elusive. There is increasing evidence, however, that TLR-mediated signals are critically involved in this process. TLRs are a group of receptors recognizing conserved molecular patterns expressed by exogenous pathogens or displayed on certain endogenous molecules. To date, 10 TLRs have been identified in the human genome, many of which are constitutively or inducibly expressed in human B cells. Stimulation of B cells with TLR ligands not only leads to cell proliferation and antibody production and class switching, but also promotes the expression of co-stimulatory molecules and secretion of various cytokines, which presumably may contribute to the enhanced capacity of B cells as MK-4827 antigen-presenting cells. Data supporting the involvement of TLRs in autoimmunity mainly come from studies using murine lupus models. A pioneering study by Marshak-Rothstein’s group demonstrated that effective activation of transgenic B cells expressing antigen receptor specific for IgG2a was only induced by IgG2a-chromatin immune complexes and requires the synergistic engagement of BCR and TLR9. Similarly, the activation of AM14 B cells by RNA and RNA containing auto-antigens was achieved only upon dual engagement of BCR and TLR7.